What Are Allergies?
An allergy occurs when your immune system incorrectly identifies a harmless foreign substance (allergen), such as inhaled dust and ingested wheat, as a threat and reacts strongly to it, causing adverse effects to your body. Allergies can cause mild discomfort, such as watery eyes and a runny nose, but it may also result in life-threatening complications such as suffocation from anaphylaxis, and chronic conditions such as asthma and eczema.
Allergies are a prevalent ailment that is estimated to affect between 10–40% of a country’s population according to the World Allergy Organisation (WAO). In Singapore, studies have reported that 4–5% of children have a food allergy and up to 40% suffer from allergic rhinitis, which is commonly referred to as hay fever. It is no wonder if you have experienced allergies yourself or have heard people around you complaining about their allergies.
Unfortunately, there is no cure for allergies but some childhood allergies may naturally disappear over time. Allergies can also be prevented by avoiding certain allergens, such as animal fur and peanuts, or controlled through medication and other treatments.
Allergens are inoffensive foreign substances commonly found in the environment, food, or in medications that have been wrongly recognized as a threat by the immune system. These allergens can enter the body either through the airways, ingestion, or skin contact to trigger an allergic reaction.
Environmental allergens are substances that are commonly present in outdoor or indoor environments and may enter the body through the respiratory tract (aeroallergens) or skin contact. At least 3700 substances have been reported to induce an allergic reaction upon inhalation or contact. These allergens include:
- Dust mites
- Animal dander
- Mould spores
- Bee venom
- Perfumes and cosmetics
- Tobacco smoke
Over-exposure, usually due to occupational exposure, to certain types of environmental allergens can result in the development of an allergy over time. For example, a baker constantly exposed to wheat flour may develop Baker’s asthma and a glove maker may develop contact dermatitis towards latex.
Any food has the potential to trigger an allergic reaction when ingested or inhaled as a powder. More than 170 different foods have been reported to cause IgE-mediated allergic reactions. However, only a small number of foods, termed “major food allergens”, cause most allergies. They include:
Other significant food allergens include protein-containing food additives and coloring agents, such as carmine and gelatin. Some allergens, especially those present in fruits and vegetables, only cause allergic reactions when eaten raw and do not trigger an allergy after the food is cooked.
Due to differences in genetics and sensitization by exposure, specific food allergies can also be more prevalent in a group of people, such as the people of a country. In European countries, there are significant occurrences of food allergies to celery, mustard, sesame, and lupine. While, in Japan, buckwheat is a common food allergen.
Medications and herbal remedies can also trigger allergic reactions in some people when taken orally, injected, or applied externally. Some drugs that have been commonly reported to cause allergic reactions are:
- Antibiotics (e.g. penicillin)
- Painkillers (e.g. aspirin and ibuprofen)
- Chemotherapy medications
- Autoimmune disease medications
Drug side-effects, overdose, and non-allergic hypersensitivity reactions may give rise to similar symptoms as allergies but should not be mistaken as drug allergies.
Allergies are caused by exposure to an allergen coupled with the complex responses of a hypersensitive immune system. An allergic person may be asymptomatic when exposed to the allergen in small doses and only display allergic reactions and symptoms when exposed past their allergy threshold, which is dependent on the health and sensitivity of their immune system. To comprehend how an immune system causes adverse allergic effects, we must first briefly understand the molecular mechanisms of an immune response.
Most of us know that our immune system is comprised of antibodies and white blood cells, but these are merely generic names that actually refer to a diverse group of molecules and cells, including immunoglobulin E (IgE), immunoglobulin G (IgG), mast cells, Type 1 (Th1) and Type 2 (Th2) helper T cells, B cells, eosinophils, and many more. The complex interplay between these cells and secreted chemicals eventually contribute to an immune response that develops immunity and exterminates viruses, bacteria, and other potentially harmful foreign substances that enter our body. However, when an immune system is hypersensitive, an immune response is developed against innately benign substances and causes harmful allergic reactions and diseases instead.
There are multiple pathways for immune responses. Most allergies are associated with the IgE-mediated response. In this pathway, the allergen that enters the body for the first time is digested and presented to a T cell which differentiates into a Th2 cell and interacts with B cells to produce IgE antibodies, instead of a Th1 cell which interacts with B cells to produce IgG antibodies. The IgE antibodies then bind to the surface of mast cells and cause an allergic reaction whenever the allergen enters the body and binds to IgE. This process is known as sensitization.
When the allergen is bound to an IgE antibody on the mast cell, the cell is prompted to release chemicals, such as histamines, leukotrienes, and platelet-activating factors, which cause the widening of blood vessels (vasodilatation), increased vascular permeability, smooth muscle contraction, and the hypersecretion of mucus. These effects show up as an acute allergic reaction characterized by immediate symptoms, such as a runny nose, swelling, or abdominal pain.
In people with atopy, there is an—often hereditary—predisposition to produce excess IgE antibodies against common environmental and food allergens, including dust mites, pollen, bee venom, animal dander, latex, peanuts, seafood, milk, and many other substances that are usually harmless. These allergens induce the IgE-mediated response that results in multiple atopic diseases, particularly allergic asthma and allergic contact dermatitis (eczema), and potentially life-threatening complications, such as anaphylaxis.
Non-atopic allergic diseases are caused by other non-IgE-mediated immune response pathways that also result in the activation of mast cells and the subsequent cascade that leads to disease. These allergic diseases may be clinically similar to atopic ones, but present different challenges as anti-IgE therapeutic treatments will not help to alleviate non-atopic allergic conditions.
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Depending on the type of allergen, symptoms may affect the skin, eyes, respiratory system, digestive system, or cardiovascular system. The occurrence, severity, and assortment of symptoms also depend on the allergen, degree of exposure to the allergen, and the individual’s tolerance of the allergen.
Symptoms can also be categorized based on the type of allergic reaction. Sudden (acute) allergic reactions are generally caused by IgE-mediated immune responses which give rise to symptoms instantaneously or within two hours after exposure to the allergen. These symptoms include:
Skin (Cutaneous) Symptoms
- Wheal-and-flare reaction
- Firm swelling (angioedema)
- Reddish discolouration (erythema)
- Itchy skin (pruritus)
- Measles-like rash (morbilliform eruption)
Eye (ocular) Symptoms
- Itchy eyes (ocular pruritus)
- Reddish eyelid (conjunctival erythema)
- Swollen eyes (periorbital edema)
- Runny nose (rhinorrhoea)
- Blocked nose
- Shortness of breath (dyspnea)
- Swelling of the larynx (laryngeal edema)
- Chest tightness
- Breathing difficulties
- Firm swelling of lips, tongue, or palate (angioedema)
- Itchy mouth (oral pruritus)
- Abdominal pain
- Reflux, nausea, or vomiting
- Accelerated heart rate (tachycardia)
- Slower than normal heart rate (bradycardia) in anaphylaxis
- Dizziness or fainting
A delayed allergic reaction may be caused by IgE-mediated or non-IgE-mediated immune responses. The symptoms of a delayed allergic reaction develop only after a longer while after exposure to the allergen or continue on from an acute allergic reaction. In addition to the symptoms mentioned above, the symptoms of a delayed allergic reaction may also include:
- Hives (urticaria)
- Eczematous rash
- Blood in stool (hematochezia)
- Irritability and food refusal with weight loss, especially in young children
Chronic allergy, or chronic immune dysfunction, refers to long-term (more than six weeks) and repeated episodes of an allergic reaction and its symptoms. These conditions include:
- Chronic hives (urticaria)
- Chronic allergic asthma
- Chronic allergic contact dermatitis (eczema)
Severe allergies can manifest into many complications and allergic diseases that can cause chronic disturbances or even result in death. Some of these complications and diseases arise due to specific allergens or are more commonly observed in young children.
Allergic Contact Dermatitis (allergic eczema)
Allergic contact dermatitis or allergic eczema is a delayed hypersensitivity reaction from skin contact with an allergen that results in a rash lasting hours to days. Some commonly associated contact allergens include nickel in jewellery and paraphenylenediamine in hair dye. Allergic eczema can also be associated with food allergies, particularly egg and milk, in children.
Allergic asthma refers to the chronic inflammation of the airways triggered by an allergen. The inflammation induces swelling of the airways and blockage from an excessive production of mucus, making it difficult to breathe. In severe cases, this can cause suffocation and death. An asthma attack may last a few minutes, hours, or days depending on the severity of the allergic reaction and exposure to the allergen. Dust mites, cockroaches, mould, pollen, and animal fur are typical allergens that trigger allergic asthma.
Anaphylaxis or anaphylactic shock is a rapid reaction that affects multiple organ systems and is characterized by breathing difficulties. Without urgent medical intervention, anaphylaxis can cause suffocation or cardiovascular collapse, resulting in death. It is a complication that can arise from an allergic reaction to any allergen but is largely observed for allergies towards peanuts, shellfish, fish, milk, and egg. Anaphylaxis may also be triggered by exercise after ingesting the allergen. Wheat, shellfish, and celery are the most common food allergens for such food-dependent, exercise-induced anaphylaxis.
Celiac disease and associated itchy skin disease (dermatitis herpetiformis) is triggered by an allergic response to gluten, which is a protein found in wheat, barley, and rye. This allergic reaction causes damage to the small intestine which can affect nutrient absorption, possibly leading to iron deficiency anemia, vitamin and mineral deficiencies, early onset osteoporosis, gallbladder malfunction, nervous system disorders, and gastrointestinal cancers.
Food protein–induced enterocolitis syndrome mainly affects infants and is the inflammation of the digestive tract due to complication of an allergic reaction to cow’s milk, soy, rice, oat, or meat. Continued exposure to the allergen results in vomiting, diarrhoea, poor growth, and lethargy. Even after avoidance of the allergen, a re-exposure will cause delayed effects (usually two hours after ingestion), such as vomiting, diarrhoea, and hypotension.
Food protein–induced allergic proctocolitis is another complication that affects infants. Proctocolitis is the inflammation of the colon and rectum, resulting in mucus-laden and bloody stools. Allergic proctocolitis is mainly caused by an allergy to breast milk.
Heiner syndrome is a cow’s milk-induced pulmonary disease in infants. Complications from the allergic reaction causes retention of fluids in the lung (pulmonary infiltrates), blood in cough (hemoptysis), vomiting, diarrhoea, lower-than-normal weight gain, anorexia, and iron deficiency anemia. Generally, the strict avoidance of cow’s milk will relieve symptoms and prevent Heiner syndrome from recurring.
Allergy Risk Factors
Having a hypersensitive immune system is usually hereditary, but the risk of developing an allergy can also be significantly influenced by health and lifestyle factors. Factors that increase the risk of developing allergies include:
- Presence of specific human leukocyte antigen (HLA) alleles
- Polymorphisms of FceRI-b
- Polymorphisms of the interleukin-4 family of cytokine genes
- Polymorphism of CD14
- Lack of allergen sensitization
- Having fewer siblings
- Excessive hygiene
- Receiving antibiotics within the first two years of life
- Lack of vaccination and prevention of disease
Diagnosing an Allergy
If you or your child experience difficulties breathing after exposure to a possible allergen, proceed to the emergency department of a hospital to receive immediate medical attention as it may be a symptom of anaphylaxis, which is a deadly complication of an allergic reaction.
If only mild symptoms are presented and you suspect an allergy, seek a consultation with a doctor for a professional diagnosis. Your doctor will ask you detailed questions about your symptoms, diet, and environment to look out for any new exposures to common allergens and deduce which could have caused your symptoms. This will be followed by various tests depending on the suspected allergen.
A prick/puncture test is generally safe for all ages and is the preferred initial test for the diagnosis of an allergy caused by aeroallergens, food, and some drugs and chemicals. As the name suggests, the test is carried out by pricking your skin with a device and exposing a small area to a series of tiny droplets of proteins, usually representing more than 50 potential allergens. If you are allergic to any of those represented allergens, an immediate or delayed wheal-and-flare reaction, which shows up as redness and swelling at the exposed area, will be observed and measured by the doctor.
Patch tests are used to diagnose possible contact allergens for a person that has experienced skin irritation (dermatitis). Small patches of up to 150 substances are applied separately onto areas spaced apart along the back and secured with hypoallergenic tape. These patches stay on for about two days and should not be washed or disturbed. On the second visit to the doctor, the patches will be removed and assessed for a positive reaction. The patch test may then be re-applied for more readings of longer durations (up to seven days) to ensure accurate results. This test is especially important for the diagnosis of allergic contact dermatitis (allergic eczema).
An intracutaneous test involves the injection of a small amount of allergen into the skin and should be conducted only after an assessment from a prick/puncture test has been made as intracutaneous tests can induce fatal allergic reactions. This test is more oftenly used for specific allergens, such as insect venoms and penicillin, and to confirm positive prick/puncture tests. After the injection, the patient should be monitored for at least 20 minutes for any immediate hypersensitivity reactions before leaving the clinic or hospital. The development of a skin papule may be indicative of a positive allergic reaction from the test, but these results should be interpreted cautiously as irritant effects could also result from the injection.
In allergy challenge tests, the suspected allergen (from the results of previous tests) is introduced to the patient in increasing doses and the patient is monitored closely for any allergic reactions for two to five hours. Challenge tests are usually only conducted if the results from previous tests are inconclusive or to test if a patient has developed tolerance to a previous allergy.
Food challenge tests for food allergies require the patient to ingest increasing amounts of the particular food item until an allergic reaction is observed, which would entail a positive result, or an upper limit is reached, which would mean that the patient is not allergic to that food item. Challenge tests for aeroallergens and medications are conducted in a similar manner, differing mainly in the method of introduction of the allergen.
Samples of bodily fluids can be used for immunoassays that detect the amount of molecules that are differentially present in IgE- and non-IgE-mediated allergic reactions. These include immunoassays for IgE, cytokines, and chemokines.
Samples from the nasal tract and mucus from the lungs (sputum) can also be used to screen for inflammatory biomarkers that are confirmatory of suspected respiratory diseases such as allergic asthma. The activity of cells involved in various immune responses can also be observed to deduce allergic reactions. A few of such tests include lymphocyte functional assays, basophil activation tests, and tests that detect the amount of eosinophils and their products.
Laboratory tests for allergies may also include tests for other immunologic diseases, such as acquired immunodeficiency syndrome (AIDS), immune-mediated gammopathies, and complement activation disorders, to assess whether an adverse immune response is indeed the result of an allergic reaction and not other underlying immune disorders.
Although there are no cures for allergies, there are medications and treatments that can be used to relieve or reduce allergic symptoms. Many medications can be used to relieve different allergy symptoms. They include epinephrine, steroids, antihistamines, and decongestants that are administered orally, topically, or through injections, nasal sprays, and nebulizers.
For people with severe allergies that can cause serious asthma or anaphylaxis, they may carry an emergency epinephrine autoinjector often referred to as an EpiPen. In the event of a severe acute allergic reaction, the immediate application of epinephrine counters life-threatening symptoms by dilating the airways, raising blood pressure, increasing heart rate, and suppressing muscle spasms. This provides more time for the patient to receive help and proper treatment in a hospital.
Histamines are released by mast cells during an allergic reaction and induce inflammation, causing many allergy symptoms such as hives (urticaria), swelling, and runny nose. Antihistamines refer to a group of drugs that inhibit histamine activity, thereby reducing symptoms. Depending on the targeted symptoms, antihistamines can be introduced in the form of eyedrops, nasal sprays, and tablets.
Only a few treatments, such as immunotherapy and anti-IgE therapy, can directly target the hypersensitive immune system that causes allergic reactions.
Allergy immunotherapy is used to increase the tolerance to an allergen by desensitizing the immune system through repeated exposure to minutely increasing doses of the allergen. The allergen may be delivered through injections in subcutaneous immunotherapy or tablets in sublingual immunotherapy. Immunotherapy has been proven to be effective in reducing the intensity of allergic symptoms and inflammation, thence reducing the need for medications.
Allergies can also subside naturally. Normally, food allergen tolerance is acquired over time for infants and young children as they grow up. For example, in a retrospective study that involved children with a history of wheat allergy, it was found that 70% of them acquired wheat tolerance by age 14. Unfortunately, the development of new allergies in adulthood can occur as well.
For allergies, it is especially true that prevention is better than cure (or treatment). The only way to avoid suffering from allergy symptoms is to avoid exposure to the allergen altogether. If you have allergies, here are some ways you can use to avoid allergens:
- Careful diet
- Indoor air purifiers
- Regular nasal wash
- Check pollen forecasts before heading outdoors
- Check ingredients of cosmetic products
- Maintain good environmental hygiene
- Avoid close encounters with animals
As allergies are caused by immune reactions, maintaining a strong immune system can increase its tolerance threshold for an allergen before triggering any symptoms. Maintaining good health in target organs, such as skin, respiratory tract, and gastrointestinal lining, can also prevent allergies by preventing an allergen from entering the body.
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